Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16α-diol

被引：5

作者：

Wai, HtooTint ^{[1
]}

Du, Kang ^{[1
]}

Anesini, Jason ^{[1
]}

Kim, Wan Shin ^{[1
]}

Eastman, Alan ^{[2
]}

Micalizio, Glenn C. ^{[1
]}

机构：

[1] Dartmouth Coll, Burke Lab, Dept Chem, Hanover, NH 03756 USA

[2] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03755 USA

来源：

ORGANIC LETTERS | 2018年 / 20卷 / 19期

基金：

美国国家卫生研究院;

关键词：

ESTROGEN-RECEPTOR-BETA; COLCHICINE BINDING-SITE; ALPHA ER-ALPHA; ANTIMITOTIC ACTIVITY; SELECTIVE AGONISTS; 2-METHOXYESTRADIOL; CHEMISTRY; CANCER; PAIN; CYCLOPROPYLCARBINYL;

D O I：

10.1021/acs.orglett.8b02689

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16 alpha-diol (VII) is described, along with structure activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI(50) = 0.2 mu g/mL (similar to 800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor agonist with potency for ER beta > ER alpha (ER beta EC50 = 21 nM), possess selective affinity to the cdc-2-like kinase CLK4 (K-d = 350 nM), and be phenotypically related to paclitaxel by an unbiased panel assessment.

引用

页码：6220 / 6224

页数：5

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